POS0784 LOW COMPLEMENT LEVELS ARE ASSOCIATED WITH HIGHER MORTALITY IN HOSPITALIZED PATIENTS WITH POSITIVE ANTIPHOSPHOLIPID ANTIBODIES
Authors: E. Itelman, M. Perelman, D. Kent, N. Bibar, G. Segal, L. Negru, A. Dagan
Journal: Annals of the Rheumatic Diseases (2022)

Background Antiphospholipid Syndrome is an autoimmune disease characterized by increased risk for vascular thrombosis (arterial and/or venous) thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies. The mechanisms by which aPLs induce thrombosis are unclear; several have been suggested, among them complement activation.(1-2) The complement system is a system of enzymes and regulatory proteins of the innate immune system that play a crucial role in the inflammatory response to various pathogenic stimuli. The complement and coagulation pathways are interconnected, and expanding evidence indicates that complement may be activated in patients with antiphospholipid syndrome (3-5). Objectives Our study was intended to better characterize the complicated relations between antiphospholipid antibodies and complement activation among hospitalized patients with antiphospholipid syndrome and its impact on short- and long-term prognosis Methods A retrospective cohort studies. Clinical and prognostic data of hospitalized patients with antiphospholipid syndrome and a measurement of complement levels (C3 or C4) were obtained. Rates of long-term mortality, one-year mortality, deep vein thrombosis (DVT), and pulmonary emboli (PE) were compared between patients with low complement levels and patients with normal complement levels. Low complement was defined as C3 &lt; 90 mg/dl or C4 &lt; 10 mg/dl. A multivariate analysis was performed to control for Anticardiolipin levels, β₂ macroglobulin levels and RVVT ratio. Results Complete data was available for 6,599 patients, of which 712 (11%) had low complement levels. The median age of the cohort was 47.7, and most of the patients were females (56%). Patients with low complement levels had significantly higher mortality rates 30% vs. 18%, p &lt; 0.001 for long-term mortality (Figure 1) and 15% vs. 5%, p &lt; 0.001 for 1 year mortality when compared to patients with normal complement levels. DVT and PE rates were similar (4% vs 3.8%, P = 0.78 and 4% vs 2.4%, P = 0.13 respectively). Results of the multivariate analysis (Table 1) were consistent and showed that patients with low complement levels had 111% higher mortality rates (CI 1.52-2.90, P &lt; 0.001). Table 1. Multivariate Analysis for long term mortality Multivariate Analysis OR (CI) p Low Complement 2.11 [1.52, 2.90] &lt;0.001 Anticardiolipin IGG 1.00 [1.00, 1.01] 0.243 Anticardiolipin IGM 0.99 [0.98, 1.00] 0.084 β₂ IGM 1.01 [1.00, 1.01] 0.017 β₂ IGG 1.00 [0.99, 1.00] 0.663 RVVT Ratio 0.99 [0.63, 1.52] 0.954 Figure 1. Cumulative 10-Year survival Conclusion In hospitalized patients with high aPLs, low complement levels are associated with significantly higher mortality rates. This finding is in correlation with recent literature, suggesting an important role for complement activation in APS. References [1]Chaturvedi S, Brodsky RA, McCrae KR. Complement in the pathophysiology of the antiphospholipid syndrome. Front Immunol. 2019 Mar 14;10:449. [2]Bu C, Gao L, Xie W, Zhang J, He Y, Cai G, et al. beta2-glycoprotein i is a cofactor for tissue plasminogen activator-mediated plasminogen activation. Arthritis Rheum. 2009 Feb;60(2):559–568. [3]Tedesco F, Borghi MO, Gerosa M, Chighizola CB, Macor P, Lonati PA, et al. Pathogenic role of complement in antiphospholipid syndrome and therapeutic implications. Front Immunol. 2018 Jun 19;9:1388. [4]Oku K, Nakamura H, Kono M, Ohmura K, Kato M, Bohgaki T, et al. Complement and thrombosis in the antiphospholipid syndrome. Autoimmun Rev. 2016 Oct;15(10):1001–1004. [5]Salmon JE, Girardi G, Holers VM. Complement activation as a mediator of antiphospholipid antibody induced pregnancy loss and thrombosis. Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii46–50. Disclosure of Interests None declared